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Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis
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| Veröffentlicht in: | Scientific reports 7(2017) Artikel-Nummer 4023, 8 Seiten |
|---|---|
| Personen und Körperschaften: | , , |
| Titel: | Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis/ Christoph Metzendorf, Anja Zeigerer, Sarah Seifert, Richard Sparla, Bahar Najafi, François Canonne-Hergaux, Marino Zerial & Martina U. Muckenthaler |
| Format: | E-Book-Kapitel |
| Sprache: | Englisch |
| veröffentlicht: |
22 June 2017
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| Gesamtaufnahme: |
: Scientific reports, 7(2017) Artikel-Nummer 4023, 8 Seiten
, volume:7 |
| Quelle: | Verbunddaten SWB Lizenzfreie Online-Ressourcen |
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| 245 | 1 | 0 | |a Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis |c Christoph Metzendorf, Anja Zeigerer, Sarah Seifert, Richard Sparla, Bahar Najafi, François Canonne-Hergaux, Marino Zerial & Martina U. Muckenthaler |
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| 520 | |a Liver cells communicate with the extracellular environment to take up nutrients via endocytosis. Iron uptake is essential for metabolic activities and cell homeostasis. Here, we investigated the role of the endocytic system for maintaining iron homeostasis. We specifically depleted the small GTPase Rab5 in the mouse liver, causing a transient loss of the entire endo-lysosomal system. Strikingly, endosome depletion led to a fast reduction of hepatic iron levels, which was preceded by an increased abundance of the iron exporter ferroportin. Compensatory changes in livers of Rab5-depleted mice include increased expression of transferrin receptor 1 as well as reduced expression of the iron-regulatory hormone hepcidin. Serum iron indices (serum iron, free iron binding capacity and total iron binding capacity) in Rab5-KD mice were increased, consistent with an elevated splenic and hepatic iron export. Our data emphasize the critical importance of the endosomal compartments in hepatocytes to maintain hepatic and systemic iron homeostasis in vivo. The short time period (between day four and five) upon which these changes occur underscore the fast dynamics of the liver iron pool. | ||
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| contents | Liver cells communicate with the extracellular environment to take up nutrients via endocytosis. Iron uptake is essential for metabolic activities and cell homeostasis. Here, we investigated the role of the endocytic system for maintaining iron homeostasis. We specifically depleted the small GTPase Rab5 in the mouse liver, causing a transient loss of the entire endo-lysosomal system. Strikingly, endosome depletion led to a fast reduction of hepatic iron levels, which was preceded by an increased abundance of the iron exporter ferroportin. Compensatory changes in livers of Rab5-depleted mice include increased expression of transferrin receptor 1 as well as reduced expression of the iron-regulatory hormone hepcidin. Serum iron indices (serum iron, free iron binding capacity and total iron binding capacity) in Rab5-KD mice were increased, consistent with an elevated splenic and hepatic iron export. Our data emphasize the critical importance of the endosomal compartments in hepatocytes to maintain hepatic and systemic iron homeostasis in vivo. The short time period (between day four and five) upon which these changes occur underscore the fast dynamics of the liver iron pool. |
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| spelling | Metzendorf, Christoph VerfasserIn (DE-588)1149853387 (DE-627)1010157884 (DE-576)496855964 aut, Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis Christoph Metzendorf, Anja Zeigerer, Sarah Seifert, Richard Sparla, Bahar Najafi, François Canonne-Hergaux, Marino Zerial & Martina U. Muckenthaler, 22 June 2017, Text txt rdacontent, Computermedien c rdamedia, Online-Ressource cr rdacarrier, Gesehen am 04.01.2018, Liver cells communicate with the extracellular environment to take up nutrients via endocytosis. Iron uptake is essential for metabolic activities and cell homeostasis. Here, we investigated the role of the endocytic system for maintaining iron homeostasis. We specifically depleted the small GTPase Rab5 in the mouse liver, causing a transient loss of the entire endo-lysosomal system. Strikingly, endosome depletion led to a fast reduction of hepatic iron levels, which was preceded by an increased abundance of the iron exporter ferroportin. Compensatory changes in livers of Rab5-depleted mice include increased expression of transferrin receptor 1 as well as reduced expression of the iron-regulatory hormone hepcidin. Serum iron indices (serum iron, free iron binding capacity and total iron binding capacity) in Rab5-KD mice were increased, consistent with an elevated splenic and hepatic iron export. Our data emphasize the critical importance of the endosomal compartments in hepatocytes to maintain hepatic and systemic iron homeostasis in vivo. The short time period (between day four and five) upon which these changes occur underscore the fast dynamics of the liver iron pool., Sparla, Richard VerfasserIn (DE-588)1046124250 (DE-627)775765643 (DE-576)399396683 aut, Muckenthaler, Martina VerfasserIn (DE-588)1046124595 (DE-627)775766496 (DE-576)173146813 aut, Enthalten in Scientific reports [London] : Macmillan Publishers Limited, part of Springer Nature, 2011 7(2017) Artikel-Nummer 4023, 8 Seiten Online-Ressource (DE-627)663366712 (DE-600)2615211-3 (DE-576)346641179 2045-2322 nnns, volume:7 year:2017, http://dx.doi.org/10.1038/s41598-017-02898-4 Verlag Resolving-System kostenfrei Volltext, https://www.nature.com/articles/s41598-017-02898-4 Verlag kostenfrei Volltext, http://dx.doi.org/10.1038/s41598-017-02898-4 LFER, LFER 2018-01-09T00:00:00Z |
| spellingShingle | Metzendorf, Christoph, Sparla, Richard, Muckenthaler, Martina, Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis, Liver cells communicate with the extracellular environment to take up nutrients via endocytosis. Iron uptake is essential for metabolic activities and cell homeostasis. Here, we investigated the role of the endocytic system for maintaining iron homeostasis. We specifically depleted the small GTPase Rab5 in the mouse liver, causing a transient loss of the entire endo-lysosomal system. Strikingly, endosome depletion led to a fast reduction of hepatic iron levels, which was preceded by an increased abundance of the iron exporter ferroportin. Compensatory changes in livers of Rab5-depleted mice include increased expression of transferrin receptor 1 as well as reduced expression of the iron-regulatory hormone hepcidin. Serum iron indices (serum iron, free iron binding capacity and total iron binding capacity) in Rab5-KD mice were increased, consistent with an elevated splenic and hepatic iron export. Our data emphasize the critical importance of the endosomal compartments in hepatocytes to maintain hepatic and systemic iron homeostasis in vivo. The short time period (between day four and five) upon which these changes occur underscore the fast dynamics of the liver iron pool. |
| swb_id_str | 496856448 |
| title | Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis |
| title_auth | Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis |
| title_full | Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis Christoph Metzendorf, Anja Zeigerer, Sarah Seifert, Richard Sparla, Bahar Najafi, François Canonne-Hergaux, Marino Zerial & Martina U. Muckenthaler |
| title_fullStr | Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis Christoph Metzendorf, Anja Zeigerer, Sarah Seifert, Richard Sparla, Bahar Najafi, François Canonne-Hergaux, Marino Zerial & Martina U. Muckenthaler |
| title_full_unstemmed | Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis Christoph Metzendorf, Anja Zeigerer, Sarah Seifert, Richard Sparla, Bahar Najafi, François Canonne-Hergaux, Marino Zerial & Martina U. Muckenthaler |
| title_in_hierarchy | Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis / Christoph Metzendorf, Anja Zeigerer, Sarah Seifert, Richard Sparla, Bahar Najafi, François Canonne-Hergaux, Marino Zerial & Martina U. Muckenthaler, |
| title_short | Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis |
| title_sort | acute loss of the hepatic endo lysosomal system in vivo causes compensatory changes in iron homeostasis |
| url | http://dx.doi.org/10.1038/s41598-017-02898-4, https://www.nature.com/articles/s41598-017-02898-4 |